A comprehensive guidelines-based approach reduces cardiovascular risk in everyday practice: the VARO study.

INTRODUCTION: The aim of study was to investigate the possibility of cardiovascular risk improvement through systematic identification of high-risk individuals and treatment in accordance with current guidelines using modern therapy in daily clinical practice. MATERIAL AND METHODS: Two hundred and sixty-three physicians participated in the study. The physicians were asked to screen for cardiovascular risk factors in patients presenting with unrelated problems and to re-evaluate the attainment of treatment goals in those with already known risk factors. Each physician enrolled up to 20 consecutive patients with hypertension and/or hyperlipidemia. A total of 3015 patients were included. Cardiovascular risk was assessed using the SCORE system. Risk factors were treated in accordance with current national guidelines. The therapy of hyperlipidemia and hypertension was preferentially based on rosuvastatin, amlodipine and valsartan. Further medication was at the discretion of the attending physician. Patients were examined at baseline and after 3 and 6 months. RESULTS: The principal result is that global cardiovascular risk decreased by 35% (from 8.9 ±6.4 to 5.9 ±4.4, p < 0.001). Systolic and diastolic blood pressure decreased by 12.5% (from 152 ±18 to 133 ±11, p < 0.001) and 11.4% (from 88 ±11 to 78 ±7, p < 0.001). The level of total cholesterol decreased 21% (from 6.3 ±1.2 to 5.0 ±0.9, p < 0.001) and the concentration of LDL-C decreased 28% (from 3.9 ±1.1 to 2.8 ±0.8, p < 0.001). HDL-C increased by 7% (from 1.43 ±0.58 to 1.53 ±0.56, p < 0.001) and triglycerides decreased by 25% (from 2.4 ±1.3 to 1.8 ±0.9, p < 0.001). Blood pressure and LDL-C target values were reached in 68% and 34%of patients, respectively. CONCLUSIONS: The VARO study demonstrates that in daily practice settings, both individual risk factors and global cardiovascular risk are significantly improved through the systematic identification of high-risk individuals and their treatment in accordance with current guidelines using modern pharmacotherapy.

[Familial hypercholesterolemia - past and present. My experiences and findings in our group of patients with familial hypercholesterolemia]. / Familiární hypercholesterolemie vcera a dnes. Vlastní zkusenosti a nálezy u naseho souboru nemocných s familiární hypercholesterolemií

Currently, the familial hypercholesterolemia (FH) rises the interest. The reason is that this genetic disorder is targeted by newly emerged and highly effective hypolipidemic agents, PCSK-9 inhibitors, lomitapid and mipomersen. Present paper discusses 2 patient study groups, before 50 years and nowadays. Although direct statistical analysis is impossible some changes in clinical features of FH might be found over the course of the time. In fact, the basic FH characteristic has not changed dramatically. Severe isolated hypercholesterolemia with total cholesterol 9-10 mmol/l, LDL-cholesterol 7-8 mmol/l and normal values of triglycerides dominates in laboratory analysis. Interestingly, the values of triglycerides increase and almost reach the pathological range in comparison to the values from the period 50 years ago. The values of HDL-cholesterol are normal. Manifestation of CHD in male patients over 40 years of age and in female patients over 50 years of age is not exceptional (rarely occur cases of myocardial infarction in third decade of age). Typical clinical manifestation of FH is xanthomatosis. The early detection and aggressive treatment in FH patients cause that xanthoma tendinosum, xanthelesma and arcus lipoides are less frequent as decades ago. Obesity, diabetes mellitus (DM) and hypertension do not belong to typical clinical sign of FH.

Lifestyle modification induced weight loss and changes of cardiometabolic risk factors including lowering of inflammatory response in obese children.

OBJECTIVES: Obesity is associated with increased inflammation which represents a link to atherosclerosis and cardiovascular disease. Lipoprotein associated phospholipase A2 (Lp-PLA2) is an independent marker of inflammation and atherosclerosis risk. To assess the impact of weight loss on metabolic markers of atherosclerosis including Lp-PLA2 we examined a group of Czech non-diabetic obese/overweight children exposed to a lifestyle intervention. PATIENTS AND METHODS: Fourty unrelated overweight/obese non-diabetic Czech children (13.7 ± 2.1 years, average BMI at baseline 29.8 ± 2.6 kg/m2) underwent 4 weeks of lifestyle modification (reduction of energy intake to age matched optimum and supervised physical activity). Anthropometrical and biochemical variables were determined at baseline and after the intervention. Lp-PLA2 mass concentration was assessed using the ELISA kit. Wilcocson's rank test and Spearman's correlation were used for statistical analysis. RESULTS: A significant decrease of BMI and waist circumference was associated with significant changes of plasma lipoprotein and glycaemia levels. Mass concentration of Lp-PLA2 at the baseline was 402 ± 94 µg/ml, after the intervention 368 ± 105 µg/ml (p=0.008). Change in Lp-PLA2 was associated with triglyceride level decrease (p=0.009). CONCLUSION: Intensive lifestyle modification leading to body weight decrease results in significant changes of plasma lipoprotein levels and, also, a drop of Lp-PLA2 levels in paediatric obese patients. However, even after the intervention Lp-PLA2 concentrations in this patient group remain elevated suggesting possible increased atherosclerosis risk in later life.

APOE polymorphism as a potential determinant of functional fitness in the elderly regardless of nutritional status.

OBJECTIVES: Life expectancy is determined by a combination of genetic predisposition (~25%) and environmental influences (~75%). Nevertheless a stronger genetic influence is anticipated in long-living individuals. Apolipoprotein E (APOE) gene belongs among the most studied candidate genes of longevity. We evaluated the relation of APOE polymorphism and fitness status in the elderly. MATERIAL AND METHODS: We examined a total number of 128 subjects, over 80 years of age. Using a battery of functional tests their fitness status was assessed and the subjects were stratified into 5 functional categories according to Spirduso´s classification. Biochemistry analysis was performed by enzymatic method using automated analyzers. APOE gene polymorphism was analysed performed using PCR-RFLP. RESULTS: APOE4 allele carriers had significantly worse fitness status compared to non-carriers (p=0.025). Multiple logistic regression analysis showed the APOE4 carriers had higher risk (p=0.05) of functional unfitness compared to APOE2/E3 individuals. CONCLUSIONS: APOE gene polymorphism seems be an important genetic contributor to frailty development in the elderly. While APOE2 carriers tend to remain functionally fit till higher age, the functional status of APOE4 carriers deteriorates more rapidly.

Prevalence of risk factors of cardiovascular diseases in men with erectile dysfunction. Are they as frequent as we believe?

OBJECTIVES: Vascular erectile dysfunction (ED) predicts future development of cardiovascular diseases (CVD). We performed a study in men seeking consultant medical advice regarding vascular ED for the first time without a history of cardiovascular disease, diabetes mellitus or renal insufficiency. Our goal was to evaluate the prevalence of CVD risk factors in this cohort of patients. Furthermore, we assessed the prevalence of asymptomatic subclinical atherosclerosis. MATERIAL AND METHODS: All study subjects underwent a thorough physical examination including anthropometric measurements. Laboratory analyses comprising assessment of lipid spectrum, liver and kidney function tests, glycaemia and glycated haemoglobin were measured using automated analysers. Intima-media thickness of carotid arteries was measured using SONOS machine and ankle-brachial index using a mini-duplex device. CVD risk was calculated by standard SCORE charts. Chi-square test, t-test and ANOVA were used for statistical analysis. RESULTS: We examined 35 men, average age 46.5 ± 9.9 years. Six (17.1%) had a positive family history of CVD, 19 (54.3%) had dyslipidemia, 10 (28.6%) were obese, 9 (25.7%) were active smokers, and 14 (40.0%) had arterial hypertension. Eighteen (51.4%) subjects had subclinical atherosclerosis as determined by ABI and CIMT assessment. CONCLUSION: Patients with vascular erectile dysfunction have similar prevalence of CVD risk factors to general population.

Impact of apolipoprotein A5 variants on statin treatment efficacy.

AIMS: Despite the fact that statin treatment efficacy is very high, there are substantial differences in treatment effectiveness among individuals. It is supposed that genetic predisposition plays an important role in these differences, but the contribution of individual polymorphisms is poorly understood. So far, more than 30 genes have been examined with ambiguous results. Apolipoprotein A5 is an important determinant of plasma lipid concentrations and its genetic variation could account for some of the observed differences in the response to statin therapy. However, this has not been analyzed before. MATERIALS AND METHODS: We examined the putative association between APOA5 SNPs (c.-1131T>C, c.56C>G and c.457G>A) and efficacy during 3 months of statin treatment in 187 adult Caucasians. Patients were treated with low-dose (10 or 20 mg per day) simvastatin (46.3%), atorvastatin (40.5%) and lovastatin (13.2%). RESULTS: The decrease in cholesterol was not significantly associated with the type or dose of statin. Carriers of the APOA5 genotype TT-1131 (n = 154) benefited more from statin treatment when compared with the C-1131 allele carriers (n = 33) (Delta low-density lipoprotein cholesterol: -36.3 +/- 15.1% vs Delta low-density lipoprotein cholesterol: -29.9 +/- 12.5%; p < 0.005, Mann-Whitney test). This result was independent of sex, age, BMI and APOE polymorphism. CONCLUSION: Our results suggest that the APOA5 gene variants may play an important role in the pharmacogenetics of statin treatment.